tbuckley/cabot-search huggingface dataset:
AB0314 MULTIMORBIDITY BURDEN IN RHEUMATOID ARTHRITIS
Authors: D. C. Varela, J. C. Sarmiento Monroy, M. J. Mantilla Ribero, C. Villota, M. Rodriguez-Jimenez, R. D. Mantilla Hernández
Journal: Annals of the Rheumatic Diseases (2022)

Background Multimorbidity in patients with rheumatoid arthritis (RA) has been described as the coexistence of two or more chronic diseases and is the most common cause of death in this population. Objectives To describe the prevalence of multimorbidity and mortality trends in a well-characterized cohort of patients with RA. Methods A retrospective cohort study of patients with RA (1987 ACR criteria) was conducted. Each patient was evaluated and followed by a rheumatologist in a single outpatient private center in Bogotá, Colombia, from 2014 to 2021. Categorical variables were expressed in frequency and percentage and quantitative variables in mean and standard deviation or median with interquartile range, depending on the distribution of the data. Statistical package: SPSS 25. Results A total of 783 patients were included. 11% of patients with RA present multimorbidity. Baseline characteristics were as follows: female gender 81.6%, mean age 51.8±11 years, mean disease duration 8 (IQR 3-15) years, RF positive 80.1%, ACPA positive 58.2%, and erosions 24.9%. Most patients have received glucocorticoids (89.8%), and conventional synthetic DMARDs (97.8%), being prednisone and methotrexate the most frequently prescribed. Hypertension was prevalent in 27.7%, osteoporosis 19.3%, malignancies in 5.5% and principal infection was urinary infection 14.3%. Polyautoimmunity was present in 5.7% most frequently Autoimmune thyroid diseases 10.6% and Sjögren syndrome 9%. After a median of 73 months of follow-up, the mortality rate was 1% of the entire cohort, being cardiovascular disease and COVID-19 infection the main causes. Conclusion Patients with RA have an important multimorbidity burden and this increased risk of adverse outcomes and mortality. References [1]Figus FA, Piga M, Azzolin I, McConnell R, Iagnocco A. Rheumatoid arthritis: Extra-articular manifestations and comorbidities. Autoimmun Rev. 2021 Apr;20(4):102776. doi: 10.1016/j.autrev.2021.102776. [2]McQueenie R, Nicholl BI, Jani BD, Canning J, Macdonald S, McCowan C, Neary J, Browne S, Mair FS, Siebert S. Patterns of multimorbidity and their effects on adverse outcomes in rheumatoid arthritis: a study of 5658 UK Biobank participants. BMJ Open. 2020 Nov 23;10(11):e038829. doi: 10.1136/bmjopen-2020-038829 Table 1. Prevalence of the diseases. Disease Prevalence Chronic disease Hypertension 27.7% Dyslipidemia 26.7% Osteoporosis 19.3% Obesity 7.7% Diabetes Mellitus 7% Cardiovascular disease Myocardial infarction 3.4% Cerebrovascular disease 1.4% Thrombosis 1.8% Infections Urinary infection 14.3% Tuberculosis 11.2% COVID-19 8.2% Autoimmune disease Autoimmune thyroid diseases 10.6% Sjögren syndrome 9% Systemic Lupus Erythematosus 2% Disclosure of Interests None declared
AB1321 THE DIAGNOSTIC DELAY IN PATIENTS WITH SCHNITZLER SYNDROME: A CASE SERIES
Authors: E. Borzova, S. Salugina, V. Rameev, V. Gorodetskiy, A. Torgashina
Journal: Annals of the Rheumatic Diseases (2022)

Background Schnitzler syndrome is a rare syndrome associated with recurrent whealing and monoclonal gammopathy. Since its first description in 1972 by the French dermatologist Prof. Liliane Schnitzler, around 500 cases have been described in Europe. The diagnostic delay in Schnitzler syndrome of 5 years was previously reported [Lipsker et al, 2001]. Despite a growing clinical experience [de Koning et al, 2014], Schnitzler syndrome presents a diagnostic challenge in clinical practice. The variation in the diagnostic delay in Europe is a subject of an ongoing systematic review by our multidisciplinary team. Objectives In this work, we would like to analyze a diagnostic delay in the patients with Schnitzler syndrome followed up at tertiary clinical and research setting. Methods We present the data from the patients with Schnitzler syndrome that have been under our care by a multidisciplinary team over a period from 2015 to 2021. All patients were analyzed for the age of disease onset and a diagnostic delay for Schnitzler syndrome. Results There are currently 14 patients with Schnitzler syndrome under our care. Of these, there were eight men and six women. The median age at the disease onset was 50.5 years, with the range from 25 to 79 years. The median diagnostic delay in our patient series was 3 years, ranging from 1 to 22 years. Noteworthy, in three patients the diagnostic delay for Schnitzler syndrome was over 5 years [6, 12 and 22 years]. Nine patients were treated with IL-1 inhibitors (iIL-1) (canakinumab and anakinra). Conclusion Our analysis suggest that the diagnostic delay remains considerable even 50 years after the initial description of this syndrome. Our data on the diagnostic delay in Schnitzler syndrome is in keeping with the clinical experience in most countries with over 5 published cases, including France, Germany, Spain, Portugal and Italy. An early recognition of Schnitzler syndrome is crucial for prompt treatment targeting IL-1. The rarity of this syndrome and a wide range of initial signs and symptoms in these patients delay the correct diagnosis and a start of the biological therapy in these patients. An increased awareness of Schnitzler syndrome may reduce the diagnostic delay in these patients. A multidisciplinary approach is essential for an early diagnosis of Schnitzler syndrome. References [1]Lipsker D et al. The Schnitzler Syndrome. Four new cases and review of the literature. Medicine. 2001; 80:37-44. [2]de Koning HD. Schniztler’s syndrome: lessons from 281 cases. Clin Transl Allergy. 2014; 4:41. Disclosure of Interests None declared
AB1166 MYOCARDITIS FOLLOWING mRNA COVID VACCINE COMPARED TO PAEDIATRIC MULTISYSTEM INFLAMMATORY SYNDROME MULTICENTER RETROSPECTIVE STUDY
Authors: Y. Butbul, K. Kaidar, P. J. Hashkes, Y. Dizitzer, I. Kanteman, Y. Berkun, E. M. Eisenstein, M. Hamad Saied, O. Goldzweig, M. Heshin-Bekenstein, E. Ling, M. Feldon, R. Tal, G. Amarilyo, L. Harel
Journal: Annals of the Rheumatic Diseases (2022)

Background Since the development of COVID 19 vaccines, more than 300 million people have been immunized worldwide. Soon after vaccinations were initiated, reports on cases of myocarditis following the second vaccine dose have emerged. Objectives This study aims to report our experience with nine patients with post COVID-19 vaccine myocarditis, and to compare them to a cohort of patients who presented with paediatric inflammatory multisystem syndrome (PIMS / PIMS-TS) post COVID 19 infection. Methods We collected all reported cases of patients who developed myocarditis following COVID 19 vaccination (Pfizer mRNA BNT162b2), from all pediatric rheumatology centers in Israel, and compared them to the cohort of patients previously diagnosed with PIMS. Results Nine patients with myocarditis post-vaccination were identified and compared to 78 patients diagnosed with PIMS. All patients with post-vaccination myocarditis were males who developed symptoms following their second dose of the vaccine. Patients with myocarditis post-vaccination had a shorter duration of stay at the hospital (4.4±1.9 vs. 8.7±4.7 days), less myocardial dysfunction (11.1% vs. 61.5%), and all had excellent outcomes as compared to chronic changes among 9.2% of patients with PIMS. Conclusion The clinical course of vaccine-associated myocarditis appears favorable, with resolution of symptoms in all the patients in our cohort. The risk–benefit decision for vaccination remains highly favorable, given the potential morbidity of patients with COVID-19, especially those with PIMS. Disclosure of Interests None declared
Ceritinib is a novel triple negative breast cancer therapeutic agent
Authors: Shengli Dong, Hassan Yousefi, Isabella Van Savage, Samuel C. Okpechi, Maryl K. Wright, Margarite D. Matossian, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
Journal: Molecular Cancer (2022)

Abstract Background Triple-negative breast cancers (TNBCs) are clinically aggressive subtypes of breast cancer. TNBC is difficult to treat with targeted agents due to the lack of commonly targeted therapies within this subtype. Androgen receptor (AR) has been detected in 12–55% of TNBCs. AR stimulates breast tumor growth in the absence of estrogen receptor (ER), and it has become an emerging molecular target in TNBC treatment. Methods Ceritinib is a small molecule inhibitor of tyrosine kinase and it is used in the therapy of non-small lung cancer patients. Enzalutamide is a small molecule compound targeting the androgen receptor and it is used to treat prostate cancer. Combination therapy of these drugs were investigated using AR positive breast cancer mouse xenograft models. Also, combination treatment of ceritinib and paclitaxel investigated using AR − and AR low mouse xenograft and patient derived xenograft models. Results We screened 133 FDA approved drugs that have a therapeutic effect of AR + TNBC cells. From the screen, we identified two drugs, ceritinib and crizotinib. Since ceritinib has a well- defined role in androgen independent AR signaling pathways, we further investigated the effect of ceritinib. Ceritinib treatment inhibited RTK/ACK/AR pathway and other downstream pathways in AR + TNBC cells. The combination of ceritinib and enzalutamide showed a robust inhibitory effect on cell growth of AR + TNBC cells in vitro and in vivo. Interestingly Ceritinib inhibits FAK-YB-1 signaling pathway that leads to paclitaxel resistance in all types of TNBC cells. The combination of paclitaxel and ceritinib showed drastic inhibition of tumor growth compared to a single drug alone. Conclusions To improve the response of AR antagonist in AR positive TNBC, we designed a novel combinational strategy comprised of enzalutamide and ceritinib to treat AR + TNBC tumors through the dual blockade of androgen-dependent and androgen-independent AR signaling pathways. Furthermore, we introduced a novel therapeutic combination of ceritinib and paclitaxel for AR negative or AR-low TNBCs and this combination inhibited tumor growth to a great extent. All agents used in our study are FDA-approved, and thus the proposed combination therapy will likely be useful in the clinic.
AB1380 ULTRASONOGRAPHIC CHANGES OF PLANTAR FASCIA IN PATIENTS WITH PLANTAR FASCIITIS DUE TO ACQUIRED FLAT FOOT
Authors: O. Turchin, A. Liabakh, O. Burianov, T. Omelchenko, L. Osadcha
Journal: Annals of the Rheumatic Diseases (2022)

Background Plantar fasciitis is a chronic degenerative process of the plantar fascia enthesis. It manifests by pain, predisposition to prolonged course and treatment resistance. In many cases, plantar fasciitis develops in patients with acquired flat feet. Taken into consideration above mentioned, the study of the plantar fascia changes in patients with acquired flat feet by sonography is relevant. Objectives To investigate the quantitative and qualitative sonographic changes of the plantar fascia in the case of plantar fasciitis in patients with acquired flat foot. Methods 190 patients with plantar fasciitis on the basis of acquired flat feet (133 females and 57 males). The average age of patients was 48 ± 0.97 years (18-81years). Unilateral pathology was noted in 117 patients and bilateral – in 73 patients. The average body mass index was 27.68±0.3. The average duration of pain syndrome was 101 ± 6.0 days (7-390 days). The pain syndrome lasted up from 1 to 6 months – in 152 patients, and more than 6 months – in 38 patients. The control group included 15 healthy volunteers (30 feet). Clinical radiological, sonographic, and statistical methods were used. Results The main sonographic features were significant reduction in echogenicity, erased or missing fibrous pattern, fuzzy contour of the aponeurosis; and modified contour of the calcaneus; small focal hyperechogenicity points in enthesis were detected. Loci of vascularization were detected using power Doppler sonography. The average thickness of plantar fascia in the study group was 6,14±1,5 mm (2,3-7,7 mm) and in control group – 3,5±0,1 mm (2,5-4,4 mm). Conclusion Sonographic signs of plantar fasciitis on the basis of acquired flat feet were changes in echogenicity and structure, changes in the contours of the cortical layer of enthesis and plantar fascia, the thickening of the enthesis of the plantar fascia of more than 4 mm. Disclosure of Interests None declared
AB0958 The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis: ultrasound study
Authors: I. Mahmoud, S. Rahmouni, A. Ben Tekaya, S. Bouden, L. Rouached, R. Tekaya, O. Saidane, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2022)

Background It has been shown that there is an anatomical link between the distal interphalangeal joint (DIP) extensor tendon enthesitis and the nail changes in psoriatic arthritis (PsA) [1]. Objectives To evaluate the relationship between nail involvement and enthesopathy at DIP level in PsA patients using ultrasonography (US). Methods We included patients with PsA. According to OMERACT, the following elemental lesions were dichotomously (presence/absence) evaluated on greyscale US assessment at extensor tendon insertion at distal phalanx of DIP joints: abnormally hypoechoic, enthesophytes, and erosions. We also measured the tendon thickness. Increased abnormal vascularization at entheseal level was also assessed using PD technique. We also performed an US assessment of the finger nails that included the study of morphological changes and measurement of the thickness of nail bed (NBT), nail plate (NPT) and adjacent skin (ST). Results We included 33 PsA patients (323 DIP). Eleven patients (34 %) presented psoriatic onychopathy (45 fingernails) with a mean NAPSI 7 (IQR (25,75)) [2 -18]. US study of the nails revealed dystrophy in 75 nails (23%). At patient level, the mean NPT, NBT and SK were 1.90±0.22, 0.38±0.09, and 2.33±0.62, respectively. None of the patients had clinical involvement of DIP. Using US, we examined 325 extensor tendon. The mean thickness of the tendon was 0.63mm ±0.1 mm. The tendon was abnormally hypoechoic in two fingers (0.61%). Erosions were present in 16 DIP (4.9%). We found enthesophytes in 82 DIP joints at insertion of extensor digitorum tendon (25.23%). We did not observe increased abnormal vascularization at entheseal level. At finger level, the extensor tendon thickness was higher in the presence of US nail dystrophy (0.70 mm vs 0.60, p=0.01). Erosions were more common in fingers with US nail involvement (14.6 % vs 1.9%, p=0.00). Osteophytes were present in 20% of fingers with US nail involvement and 26.3% of fingers without US nail involvement (p=0.166). The thickness of DIP digital extensor tendons was correlated with the NBT(r = 0.412, p = 0.00), the NPT (r = 0.310, p = 0.00), and the thickness of the adjacent skin (r = 0.509, p = 0.00). Conclusion The presence of US nail dystrophy was associated with thicker extensor tendon and more erosions. The thickness of the tendon was correlated with the thickness of the nail parts. This might be explained by the close relationship between nail and enthesis and supports the theory of the enthesis as an extended organ beyond the tendon bony attachment. References [1]Tan, A. L .et al (2006). Rheumatology, 46(2), 253–256. Disclosure of Interests None declared
AB1278 INCIDENCE OF ENDOCRINE AND EXOCRINE INSUFFICIENCY IN PATIENTS WITH AUTOIMMUNE PANCREATITIS AT DIAGNOSIS AND AFTER TREATMENT
Authors: M. Lanzillotta, M. Tacelli, G. Capurso, L. Dagna, E. Della Torre
Journal: Annals of the Rheumatic Diseases (2022)

Background Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that may lead to endocrine and exocrine insufficiency if left untreated. AIP clinically responds to glucocorticoids (GCs) therapy, but multiple GCs courses are often required to maintain remission with potential detrimental effects on glycaemic control. To date, data on pancreatic function in AIP are scanty and heterogeneous. Objectives We aimed to assess the rate of endocrine and of exocrine insufficiency at diagnosis and at follow up in patients with AIP as well as the impact of GC therapy on pancreatic function in the long term. Methods The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to August 2021 to identify studies reporting data on endocrine and exocrine insufficiency in patients with type 1or type 2 AIP. Studies involving ≥ 3 patients were selected. In case of duplicated studies, the most recent or the one with the largest sample were included. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effect model and expressed in terms of pooled prevalence rates. Results A total of 6522 AIP patients and sixty-two studies were included in the analysis. The pooled estimate rate for the overall prevalence of diabetes in AIP at baseline (combined type 1 and type 2 AIP) was 36.9% (95% CI 31.9-41.9, I 2 96.1%). The pooled estimate for the prevalence of diabetes was 44.3% (95%CI 39.1-49.4, I 2 91.9%) in type 1 AIP and 11.3% (95%CI 6.1-16.6, I 2 42.5%) in type 2 AIP (p &lt; 0.01), respectively. The pooled prevalence rate of exocrine insufficiency was 45.2% (95%CI 32.9-57.4; I 2 97.4%). The pooled estimate rate of diabetes at follow-up was 44.2% (95%CI 26.1-62.4) in studies where GCs were given to 100% of patients and 41.8% (95%CI 30.6-52.9) in studies where GCs were given to less than 100% of patients. The pooled prevalence of pancreatic exocrine insufficiency was 36.2% (95%CI 20.4-52.0, I 2 96.4%). Conclusion A large proportion of patients with AIP displays concomitant exocrine and endocrine insufficiency at the time of diagnosis. The incidence of diabetes at the longest available follow up tends to increase in patients treated with GCs. Further long-term studies are warranted to assess the impact of GCs and immunosuppressive treatments on glycaemic control and on exocrine pancreatic function. References [1]Löhr JM, Beuers U, Vujasinovic M, et al. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J. 2020;8:637-666. [2]Lanzillotta M, Vinge-Holmquist O, Overbeek KA, et al.PrescrAIP: A Pan-European Study on Current Treatment Regimens of Auto-Immune Pancreatitis. Front Med. 2020 Aug 5;7:408. Disclosure of Interests None declared
AB0037 APE1 REGULATES THE MIGRATION OF FIBROBLAST-LIKE SYNOVIOCYTES FROM PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: H. R. Lee, J. Kim, S. J. Yoo, J. A. Park, H. K. Joo, Y. R. Lee, S. Kim, B. H. Jeon, S. W. Kang
Journal: Annals of the Rheumatic Diseases (2022)

Background The level of apurinic/apyrimidinic endonuclease 1 (APE1) is elevated in synovial fluids from patients with rheumatoid arthritis (RA). However, the role of APE1 in RA pathogenesis remains unclear. Objectives To explore whether APE1 affects cell migration through reactive oxygen species (ROS) level, fibroblast-like synoviocytes (FLS) from patients with RA were stimulated with human recombinant APE1. Methods Synovial tissues were obtained from RA patients who were undergoing synovectomy or joint replacement. The isolated cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum and maintained in a 5% CO 2 incubator at 37 °C. FLS were used for experiments after three to six passages. Cells were stimulated with or without recombinant interleukin 17 (IL-17; 10 ng/ml), tumor necrosis factor alpha (TNF-α; 10 ng/ml), and long-lasting recombinant human APE1 (MR201; 1, 10, 100 ng/ml) for 24 h. ROS levels were analyzed using MitoSOX dye. Cell migratory ability was examined using wound migration assay. Results RA FLS treated with APE1 showed slightly decreased level of mitochondrial specific ROS. To induce pro-inflammatory conditions, RA FLS were incubated with IL-17 and TNF-α. These cytokines are highly detected in RA synovium and directly stimulate FLS activation. Stimulation with IL-17 and TNF-α upregulated ROS by 30% compared to control. Cytokines-induced increase of ROS was inhibited by 22% in APE1 treatment. When FLS cultures were approximately 90% confluent, FLS monolayers were wounded with pipette tips and treated with IL-17/TNF-α and APE1 for 24 h. Cell migration was increased after treatment with IL-17/TNF-α. Cytokines-induced cell migration was remarkably attenuated by APE1 treatment. Conclusion Recombinant APE1 markedly inhibited mitochondrial specific ROS production and IL-17/TNF-α-induced cell migration in RA FLS. References [1]Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–55. [2]Mateen S, Moin S, Khan AQ, Zafar A, Fatima N. Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS One. 2016;11(4):e0152925. [3]Lefevre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnaker EM, Tarner IH, Robbins PD, et al. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. 2009;15(12):1414–20. Acknowledgements This research was supported by Chungnam National University Hospital Research Fund, 2021. Disclosure of Interests None declared
AB1054 FERRITIN LEVELS IN PATIENTS WITH GOUT AND COMORBID PATHOLOGY
Authors: G. Kuzmina, O. Lazarenko
Journal: Annals of the Rheumatic Diseases (2022)

Background Gouty arthritis is the most common type of inflammatory arthritis among the working-age population. In patients with gout, the following comorbidities are often recorded: hypertension, diabetes mellitus, and heart failure. The issue of the relationship between ferritin levels in patients with gout and comorbid pathology remains relevant, as well as establishing the nature of this relationship. Objectives The aim of this study was to determine the frequency of hyperferritinemia in patients with gout and comorbid hypertension. Methods 122 patients with hypertension, middle age of whom amounted to 56.0 (10.29) years, had been surveyed, 104 (85.2 %) men and 18 (14.8 %) women. All patients were divided into three groups: the main group – 72 patients with hypertension in combination with gout, comparison group – 50 patients with hypertension without gout, control group – 20 patients with gout. Standard clinical examination and laboratory evaluation including ferritin, uric acid levels were performed. Results The following ferritin values were determined in the main group 344.0 (196.5; 389.0) ng/ml, comparison group 130.9 (68.0; 143.3) ng/ml, control group 276.5 (257.0; 354.5). The ferritin level were significantly higher in the main group - 2.6 (p &lt;0.01) times than in the comparison group. The ferritin level were significantly higher in the control group - 2.1 (p &lt;0.01) times than in the comparison group. There is no significant difference the ferritin levels between main and control groups (p&gt; 0.05), which indicates the important role of this marker in gout and requires further study of hyperferritinemia in gout and comorbid pathology. Conclusion The combination of hypertension with gout in patients was associated with a higher ferritin levels, which should be considered not only in the context of chronic inflammation, but as part of the disease with the possibility of further determining the cause and diagnostic value of hyperferritinemia in this category of patients. References [1]Fatima T, McKinney C, Major TJ, et al. 2018. The relationship between ferritin and urate levels and risk of gout. Arthritis Research &amp; Therapy, 20 (1), 179. https://doi.org/10.1186/s13075-018-1668-y . [2]Sandnes M, Ulvik RJ, Vorland M, Reikvam H. 2021. Hyperferritinemia – A Clinical Overview. J Clin Med, 10 (9), 2008. doi: 10.3390/jcm10092008. Disclosure of Interests None declared